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能量压力诱导的circZFR通过调节替代拼接来增强肺腺癌中的氧化酸化
Zhifei Ma1,2, Hao Chen1,3, Zhijun Xia1,4
1Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 21009, P.R. China.
Journal of experimental & clinical cancer research : CR
|July 17, 2023
概括
循环RNA ZFR (circZFR) 通过增强氧化酸化来促进在能量压力下肺腺癌的生存. 在瘤中升高的循环ZFR与预后不佳相关,提供了潜在的治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 代谢过程中的代谢.
背景情况:
- 循环RNAs (circRNAs) 与癌症有关.
- 肺腺癌 (LUAD) 在能量压力下代谢重编程中circRNAs的作用尚不清楚.
研究的目的:
- 为了研究 circRNAs 在 LUAD 代谢适应能量压力的功能和机制.
- 为了确定LUAD的潜在治疗点.
主要方法:
- 循环RNA分析和葡萄糖剥夺测试以确定能量压力诱导的循环RNA.
- 用RNA-seq,RTCA和OCR测量来评估LUAD中的circZFR功能.
- 涉及circRNA pull-down,RNA免疫沉和生物信息学的机制研究.
- 在LUAD组织和患者衍生的异种移植中进行临床验证.
主要成果:
- 循环ZFR在LUAD上调并由葡萄糖剥夺诱导,增强氧化酸化 (OXPHOS) 以适应能量压力.
- CircZFR表达与较高的T阶段和LUAD患者的更差预后有关.
- CircZFR稳定了HNRNPLL,调节了替代拼接,并激活了AKT-mTOR通路以促进OXPHOS.
结论:
- CircZFR在LUAD对能量压力的代谢适应中发挥着关键作用.
- 在LUAD中,CircZFR代表了抗癌代谢疗法的潜在新目标.
- 这项研究增强了对癌症代谢中的circRNAs和替代拼接的理解.
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